The goal of the proposed research is to understand the structural basis of recognition of viral antigens and synthetic peptides by the immune system. In particular, the proposal is to determine the three-dimensional structures by x-ray crystallography of an anti-peptide Fab, and Fab- peptide complex and a Fab- protein complex to understand recognition of the same antigenic determinant in a pepetide and in a protein. This nine amino acid determinant (98-106 HA1) has been shown by several antipeptide monoclonal antibodies to be the major immunodominant site of a 36 amino acid synthetic immunogen corresponding to sequence 75-110 of the A/Vic/3/75 strain of influenza virus haemagglutinin (HA1). The conformation of this determinant has been analyzed in the structure of the solved Hong Kong HA structure and in solution by NMR. The main goals are to determine the following structures for a complete description of the antibody-antigen recognition. 1. Crystal structure of antipeptide Fab. The three dimensional structure will be determined from the currently available x-ray data quality crystals of a monoclonal Fab raised against a 36 amino acid synthetic peptide corresponding to residues 75-110 of A/Vic/3/75 haemagglutinin (HA1) of influenza virus. 2. Crystal structure of a Fab- peptide complex. Crystals of the Fab will be soaked in solutions of various synthetic peptides (about 97-108 HA1, Ka 10-6 - 10-8) and the currently available crystals grown from a mixture of the Fab and peptide (88-110 HA1) will be used to determine the Fab- peptide complex structure. 3. Crystal structure of an Fab- protein. Crystallization conditions of mixtures of the anti-peptide Fab and the HA1 "tops" (HA1 27-328. Ka about 10-6 - 10-7) will be sought to obtain large single crystals of the complex. Structural studies of suitable crystals will be initiated.